Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 1/6/2026 with respect to the amino acid sequence disclosures have been fully considered but they are not persuasive.
Per MPEP 2422 and 37 CFR 1.821, any amino acid sequences with at least 4 or more specifically defined and enumerated residues and therefore requires a SEQ ID NO. Even if the amino acid sequences of Tables 2 and 3 are not claimed in the application, each still requires a SEQ ID NO. Also see “Nucleotide and/or Amino Acid Sequence Disclosures” and Specification sections below.
Applicant’s arguments, filed 1/6/2026 with respect to the rejection(s) of claim(s) 1, 2, 4, 5, and 11 under 35 U.S.C. 112 and 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of restriction withdrawal (see below).
Election/Restrictions
Claims 2, 4, 5, and 13 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 6 and 8-10, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 6/9/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Status
Claims 2, 4-6, 8-10, and 13 are pending. Claims 2 and 4 are currently amended. Claims 1, 3, 7, 11, and 12 are cancelled. Claim 13 is new.
Priority
The application is the 371 national stage entry of PCT/JP2020/024869, filed 6/24/2020, which claims priority to the provisional application 62/870,629, filed 7/3/2019. The priority date of 7/3/2019 is acknowledged.
Information Disclosure Statement
The information disclosure statement filed 9/23/2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825. This application contains a “Sequence Listing” as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)). A copy of the "Sequence Listing" in computer readable form (CRF) has been submitted; however, the content of the CRF does not comply with one or more of the requirements of 37 CFR 1.822 through 1.824, as indicated in the "Error Report" that indicates the "Sequence Listing" could not be accepted. Refer to attachment or document "Computer Readable Form (CRF) for Sequence Listing – Defective" dated 1/6/2026.
Required response – Applicant must provide:
A replacement "Sequence Listing" part of the disclosure, as described above in item 1); together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter and
An amendment to the specification to remove the “Sequence Listing previously submitted as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3))
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, Applicant must also provide:
A CRF in accordance with 1.821(e)(1) or 1.821(e)(2) as required by 37 CFR 1.825(b)(6)(ii); and
Statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Tables 1, 2 and 3 and compounds I-3 through I-6 ([0153-0162]) depict/list sequences without SEQ ID NO’s.
Specification
The disclosure is objected to because of the following informalities: The specification recites amino acid sequence with 4 or more specifically defined and enumerated residues and therefore requires a SEQ ID NO. However, no SEQ ID NO is listed in the claim. See MPEP 2422 and 37 C.F.R. 1.821. Appropriate correction is required.
Claim Objections
Claim 2 is objected to because of the following informalities: line 6 recites that “the N-terminal amino acid residue is a chloroacetylated” (emphasis added). Amend the claim such that it reads “the N-terminal amino acid residue is chloroacetylated”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-6 and 8-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 4 and 5 recite a chemical compound comprising the CD38-binding peptide of claim 2 wherein the peptide further comprises a linker moiety, specifically PEG in claim 5. The scope of these claims is indefinite as it is unclear what, if anything, the linker/PEG moiety attaches to, and a chemical compound is not described or explained in the instant specification.
Claim 6 depends from claim 1, which is cancelled. Thus, the scope of claim 6 is indefinite. For purposes of examination, claim 6 is being interpreted as if depending from claim 2. Further, by virtue of their dependency on claim 6, claims 8-10 are also hereby rejected for this same reasoning.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
First rejection
Claim 6 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a subset of CD38-associated cancers, does not reasonably provide enablement for treating all/any CD38-associated cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The invention is a method of
treating a CD38-associated cancer comprising administering to a subject in need thereof a pharmaceutical composition comprising the CD38-binding peptide of claim 1 (interpreted as a peptide of claim 2), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.
The claim is written such that the breadth includes any cancer with any degree or amount of association to CD38, no matter how extensive or how limited. The issue is the degree of association required between CD38 and said cancer, and whether cancers with limited or indirect association can be treated by practicing this method.
2) State of the prior art and 4) predictability or unpredictability of the art: At the time of
filing, the art recognized that CD38 was instrumental to the progression of certain hematological cancers but its role in solid tumors was less defined.
For instance, Konen (Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors. Cells. 2019 Dec 24;9(1):52.) teaches that CD38 has been extensively studied for its role in hematological malignancies, including chronic lymphocytic leukemia and multiple myeloma (Pg 2, second paragraph; Pg 5, “4.1 Hematological Malignancies”); the instant specification similarly teaches that hematological malignancies have increased expression of CD38, in particular chronic lymphocytic leukemia and acute promyelocytic leukemia ([0006, 0009, 0069, 0071]). There are also reports indicating upregulation of CD38 in immune and/or tumors cells that contribute to the progression of esophageal, advanced colorectal, glioma, cervical, and lung cancer (Pg 6, “4.2 Solid Tumors”).
However, not all cancers are associated with an increase in CD38; Konen teaches that low expression of CD38 enriches for luminal progenitor cells in prostate cancer, which are prognostic for biochemical recurrence and metastasis (Pg 7, “4.2 Solid Tumors”). Would a tumor with low expression of CD38 be treatable with a CD38-binding peptide as recited in the instant method claim?
Konen states that the understanding of how CD38 may influence the progression and immune evasion within solid tumors is a relatively new field. In solid tumors, the data largely indicate an immunosuppressive role for CD38 indicating the potential to utilize CD38 inhibitors in these tumors. However, the implementation of a CD38-targeting strategy
in solid tumors would likely be more complicated than it may first appear. Far from inhibiting a simple enzymatic reaction, CD38 inhibition would likely have unforeseen effects, as it is a highly complex molecule capable of numerous functions. Additional research is required in order for the rational and efficacious delivery of these inhibitors, either alone or in combination with other immunotherapeutic agents, to fully realize their potential (Pg 2, second paragraph).
Thus, one skilled in the art would reasonably predict that the CD38-binding peptides of the instant invention could treat certain types of cancers, described above, but not broadly any cancer associated with CD38.
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable one to administer a CD38-binding peptide as recited in claim 2 to treat the breadth of CD38-associated cancers as claimed.
7) The presence or absence of working examples: The instant specification does not
provide any examples of treating CD38-associated cancers.
8) The quantity of experimentation necessary: As no working examples are disclosed in
the instant specification and only a few in the prior art, reasonable guidance with respect to treating CD38-associated cancers through administration of a CD38-binding peptide as recited in claim 2 was limited. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively treat all CD38-associated cancers.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention for the treatment of all CD38-associated cancers.
Second rejection
Claims 6 and 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a subset of CD38-associated cancers, does not reasonably provide enablement for preventing CD38-associated cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The claims are drawn to a
method of treating a CD38-associated cancer comprising administering to a subject in need thereof a pharmaceutical composition comprising the CD38-binding peptide of claim 1 (interpreted as a peptide of claim 2), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.
The instant specification defines treat, treatment, or treating to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of, and/or reduce incidence of one or more symptoms or features of a disease, disorder, and/or condition ([0052]). Effectively, the definition of treatment also reads on prevention, and the claims are not enabled for a method of preventing a CD38-associated cancer.
2) State of the prior art and 4) predictability or unpredictability of the art: The state of the art at the time of filing did not recognize that cancer could be prevented. There are several examples, discussed below, that suggest that therapeutic prevention might be possible someday but is presently not an option.
One such example is Cuzick et al. (Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003 Jan 25;361(9354):296-300.). Cuzick teaches that tamoxifen can reduce the risk of ER-positive breast cancer. However, Cuzick does not recommend tamoxifen as a preventive agent because continued research into specific subgroups of high-risk but healthy women is first needed (Pg 299, second column, first paragraph).
As another example, Schiffman et al. teach that primary prevention through vaccination against HPV might be possible in young women (Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med. 2005 Nov 17;353(20):2101-4.; Pg 2101, third column, first paragraph). However, they also teach that vaccine evaluations are ongoing (Pg 2103, third column, first paragraph). In addition, the most promising vaccines designed against HPV types 16 and 18 would only prevent 70 percent of cervical cancer cases at best (Pg 2103, second column, first paragraph). Therefore, there is still no vaccine that can definitively prevent cancer.
Other promising candidates for cancer prevention include tumor-associated antigen vaccines (Evans TR, Kaye SB. Vaccine therapy for cancer--fact or fiction? QJM. 1999 Jun;92(6):299-307.) and lunasin, a soy-derived peptide (Hernández-Ledesma B, Hsieh CC, de Lumen BO. Lunasin, a novel seed peptide for cancer prevention. Peptides. 2009 Feb;30(2):426-30.; Abstract.).
However, in each of these studies, the authors indicate that additional research is required before such they can be greenlit as preventative therapeutics.
Thus, one skilled in the art would reasonably predict that a composition comprising the instant AGM peptide or conjugate thereof would be unable to prevent cancer.
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable a composition for preventing cancer as claimed.
7) The presence or absence of working examples: As stated above, the instant
specification does not provide any examples of treating, let alone preventing, CD38-associated cancers.
8) The quantity of experimentation necessary: As no working examples are disclosed in
either the instant specification or the prior art, reasonable guidance with respect to preventing CD38-associated cancers through administration of a CD38-binding peptide as recited in claim 2 was lacking. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively treat all CD38-associated cancers.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the method of preventing a CD38-associated cancer through administration of a CD38-binding peptide of claim 2.
Allowable Subject Matter
The SEQ ID NO: 2-34 are allowable. The closest art is Rastelli et al. (WO2020132588A1, effectively filed 12/20/2018), which anticipates the instant SEQ ID NO: 1 as well as a chemical compound thereof further comprising PEG (see previous Office Action). However, SEQ ID NO: 1 has been cancelled, and Rastelli does not teach modifying SEQ ID NO: 1 to arrive at the remaining peptides SEQ ID NO: 2-34. Moreover, the remaining peptides SEQ ID NO: 2-34, relatively to SEQ ID NO: 1, exhibit one or more non-conservative substitutions that would not be obvious to make to one of ordinary skill in the art. Therefore, SEQ ID NO: 2-34 are novel and nonobvious.
Conclusion
Claims 2 is objected to; because claim 2 is not allowed, claim 13 is also objected to.
Claims 4-6 and 8-10 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara E Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658